title: Multiple antigen peptide mimetics containing gp41 membrane-proximal external region elicit broad neutralizing antibodies against human immunodeficiency virus type 1 in guinea pigs.
abstract: Eliciting a broadly neutralizing antibody response against the HIV-1 membrane-proximal external region (MPER) mimicking the activity of 4E10 and 2F5 monoclonal antibodies remains a major challenge. In this study, two novel tetra-branched peptide immunogens, 4E10- and 2F5-MAP4, were designed and synthesized using a MAP system. Guinea pigs were immunized with either of these two synthetic immunogens emulsified in an oil-phase adjuvant at 3-week intervals. After four immunizations, epitope-specific antibody responses were induced successfully, and moderate neutralizing activities against tier 1 (clades B, BC, AE) and tier 2 (clade C) HIV-1 pseudoviruses were detectable in unfractionated sera and purified IgGs. The synthetic gp41 membrane-proximal external region peptide mimetics, 4E10- and 2F5-MAP4, assisted by an appropriate adjuvant, are promising prophylactic vaccine candidates potentially capable of eliciting broadly neutralizing antibody responses against HIV-1.
authors.affiliation: National Engineering Laboratory of AIDS Vaccine, College of Life Science, Jilin University, Changchun, China.
authors.forename: Lishuang
authors.initials: L
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Miao
authors.forename: Xin
authors.initials: X
authors.lastname: Gong
authors.forename: Huayan
authors.initials: H
authors.lastname: Zhang
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Shi
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Chunlai
authors.initials: C
authors.lastname: Jiang
authors.forename: Yaming
authors.initials: Y
authors.lastname: Shan
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D000956:Antigens, Viral / Q000276:immunology; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D006168:Guinea Pigs; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D018716:Molecular Mimicry; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology; D014611:Vaccination
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D010446:Peptide Fragments; C514787:gp41 protein, Human immunodeficiency virus 1
keywords: HIV-1 vaccine; MPER; broad neutralization; multiple antigen peptide mimetics